Engineers from MIT have designed a new type of vaccine that could potentially be used to prevent HIV and malaria safely and much more effectively. These new particles are described in the February 20 issue of Nature Materials.
The particles are formed out of concentric spheres made of fat. They carry synthetic versions of virus protein particles in their core. These nano-sized lipid-based vaccines can elicit the same strong immune response as a live virus vaccine, but are much safer due to their synthetic virus particles.
Vaccines work by priming your immune system. By exposing the immune system to an infectious agent, it can more easily recognize and destroy the same pathogen during a later encounter. Vaccines are designed to incite the production of either T cells (which destroy infected cells) or B cells (which secrete antibodies to target pathogens).
However, a vaccine for HIV — much like those for polio and smallpox — requires the activation of a subset of T cells called the killer T cells, using a weakened or disabled virus. Creating an HIV vaccine using a live virus is difficult because it is hard to render it harmless.
Some vaccines, like the diphtheria vaccine, can use recombinant or synthetic proteins, or molecules normally made by the virus. However, this route is inadequate for HIV or Hepatitis B vaccines, because the synthetic particles don’t elicit the same strong T cell response.
Recently, scientists have tried working with the idea of encasing these synthetic vaccines in liposomes, or fatty droplets, which resemble normal viruses and can help stimulate killer T cells. Normally, however, these fatty droplets are unstable in bodily fluids.
Postdoctoral fellow James Moon, associate professor Darrell Irvine, and their colleagues at the Massachusetts Institute of Technology have developed a more stable way to assemble liposome nanoparticles. The virus antigen particles are packaged in multiple concentric liposomal spheres. The headgroups of adjacent lipid bilayers are then crosslinked, a technique to make them more stable and less likely to break down upon injection. The lipid bilayer structure allows these nanoparticles to be absorbed by your cells. Once inside, the harmless synthetic virus particles are released in the presence of enzymes that break down fat, called endolysosomal lipases. This provokes the killer T-cell response.
Moon and his colleagues used these nanoparticles to test the T-cell response in mice, to a protein called ovalbumin. They found that, after three immunizations using low doses of the vaccine, up to 30 per cent of all killer T cells in the mice were specific to the vaccine protein.
These results are comparable to vaccines that use live viruses, but they are much safer to prepare and use. The vaccines also elicited a strong antibody response. Researchers have yet to discover whether these vaccines can elicit the same strong response in humans.
So far, these newly constructed nano-sized lipid based vaccines are making for a potential safe delivery system for vaccines against hard-to-handle viruses like HIV or hepatitis B. Irvine and his colleagues have since moved on to try and develop these vaccines to immunize people against malaria, HIV, and cancer.
